Abstract
Fibrotic diseases cover a spectrum of systemic and organ-specific maladies that affect a large portion of the population, currently without cure. The shared characteristic these diseases feature is their uncontrollable fibrogenesis deemed responsible for the accumulated damage in the susceptible tissues. Idiopathic Pulmonary Fibrosis, an interstitial lung disease, is one of the most common and studied fibrotic diseases and still remains an active research target. In this study we highlight unique and common (i) genes, (ii) biological pathways and (iii) candidate repurposed drugs among 9 fibrotic diseases. We identify 7 biological pathways involved in all 9 fibrotic diseases as well as pathways unique to some of these diseases. Based on our Drug Repurposing results, we suggest captopril and ibuprofen that both appear to slow the progression of fibrotic diseases according to existing bibliography. We also recommend nafcillin and memantine, which haven’t been studied against fibrosis yet, for further wet-lab experimentation. We also observe a group of cardiomyopathy-related pathways that are exclusively highlighted for Oral Submucous Fibrosis. We suggest digoxin to be tested against Oral Submucous Fibrosis, since we observe cardiomyopathy-related pathways implicated in Oral Submucous Fibrosis and there is bibliographic evidence that digoxin may potentially clear myocardial fibrosis. Finally, we establish that Idiopathic Pulmonary Fibrosis shares several involved genes, biological pathways and candidate inhibiting-drugs with Dupuytren’s Disease, IgG4-related Disease, Systemic Sclerosis and Cystic Fibrosis. We propose that treatments for these fibrotic diseases should be jointly pursued.
Highlights
Fibrotic diseases constitute a group of incurable maladies that are recognized by a fibrotic phenotype affecting various organs and tissues
We identify the LCN2 gene being over-expressed in Idiopathic Pulmonary Fibrosis (IPF), Cystic Fibrosis (CF), Schistosomiasis and Systemic Sclerosis (SSc) and the FBLN1 gene being under-expressed in CF, Myelofibrosis, Polycystic Kidney Disease and SSc and over-expressed in IgG4-related Disease
Takahashi et al study the LCN2 expression in (i) the skin of patients with SSc, (ii) bleomycin-treated mice, and (iii) Fli1-deficient endothelial cells. Their experiments show that LCN2 is associated with dermal fibrosis in early Diffuse Cutaneous SSc cases but not with interstitial lung disease (ILD) markers such as diffusion lung capacity for carbon monoxide or vital capacity [40]
Summary
Fibrotic diseases constitute a group of incurable maladies that are recognized by a fibrotic phenotype affecting various organs and tissues. Pertinent mechanisms escape the homeostatic signals and due to over-repairing, cause tissue scarring. Drug repurposing on fibrotic diseases a PhD Student fellow position funded by the European Commission Research Executive Agency Grant BIORISE (No 669026), under the Spreading Excellence, Widening Participation, Science with and for Society Framework. Spyrou holds the Bioinformatics ERA Chair Position funded by the European Commission Research Executive Agency (REA) Grant BIORISE (Num 669026), under the Spreading Excellence, Widening Participation, Science with and for Society Framework
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